Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis
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DOI：
10.1016/j.ccr.2006.02.019
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发表时间：
2006-03-01
期刊：
影响因子：
50.3
通讯作者：
Aldape, K
中科院分区：
文献类型：
--
作者：
Phillips, HS;Kharbanda, S;Aldape, K
以前未描述的高级别星形细胞瘤的预后亚类被确定和发现类似于神经发生的阶段。显示神经元谱系标志物的一种肿瘤类别显示更长的存活期，而富集神经干细胞标志物的两种肿瘤类别显示同样短的存活期。预后不良的亚类表现出增殖或血管生成和间充质的标志物。复发后，肿瘤经常向间充质亚类转移。区分肿瘤亚类的基因的染色体位置在亚类之间存在平行的DNA拷贝数差异。肿瘤亚型分子标记的功能相关性由细胞系标记预测神经球生长的能力提出。利用PTEN和DLL3表达的稳健的双基因预后模型表明，Akt和Notch信号传导分别是预后不良与预后较好的胶质瘤的标志。
Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.